Selected Recent PublicationsJun 2019Pinneh, E. C., Mina, J. G., Stark, M. J. R., Lindell, S. D., Lumen, P., Knight, M. R., Steel, P. G. and Denny, P. W The identification of small molecule inhibitors of the plant inositol phosphorylceramide synthase which demonstrate herbicidal activityScientific Reports 9: 8083 (doi.org/10.1038/s41598-019-44544-1) PMID: 31147620 AbstractView PublicationJun 2019Krutyhołowa, R., Hammermeister, A., Zabel, R., Abdel-Fattah, W., Reinhardt-Tews, A., Helm, M., Stark, M. J. R., Breunig, K. D., Schaffrath, R. and Glatt, S. Kti12, a PSTK-like tRNA dependent ATPase essential for tRNA modification by Elongator.Nucleic Acids Research 47: 4814-4830 (doi.org/10.1093/nar/gkz190) PMID: 30916349 AbstractView PublicationJun 2019Trunk, K., Peltier, J., Liu, Y. -C., Dill, B. D., Walker, L., Gow, N. A. R., Stark, M. J. R., Quinn, J., Strahl, H., Trost, M. and Coulthurst, S. J. The Type VI secretion system deploys anti-fungal effectors against microbial competitorsNature Microbiol. 3: 920-931 (doi 10.1038/s41564-018-0191-x) PMID: 30038307 AbstractView PublicationNov 2017Makrantoni V, Ciesiolka A, Lawless C, Fernius J, Marston A, Lydall D, Stark MJR. A Functional Link Between Bir1 and the Saccharomyces cerevisiae Ctf19 Kinetochore Complex Revealed Through Quantitative Fitness Analysis PMID: 28754723 AbstractView PublicationNov 2015Abdel-Fattah, W., Jablonowski, D., Di Santo, R., Thuring, K. L., Scheidt, V., Hammermeister, A., Ten Have, S., Helm, M., Schaffrath, R. and Stark, M. J. Phosphorylation of Elp1 by Hrr25 is required for Elongator-dependent tRNA modification in yeast PMID: 25569479 AbstractView Publication Elongator-dependent tRNA wobble uridine modification Most processes required for the function and the survival of cells are carried out by proteins, polymers made up of building blocks termed amino acids. Small RNA molecules (tRNAs) are used to shuttle amino acids to the cellular machinery that synthesises proteins. Our interest is in a mechanism that affects the efficiency with which some of the tRNAs function. We would like to understand whether cells can use this mechanism to change the spectrum of proteins that they make. Over the past 29 years my laboratory has used the yeast Saccharomyces cerevisiae as a model organism for investigating processes that are important for cell growth and division. My current focus is on Elongator, a protein complex containing six different polypeptides that is responsible for chemical modification of uridine residues present at the ‘wobble’ position of the anticodon (U34) in a subset of tRNAs. These Elongator-dependent modifications to U34 (termed mcm5U and ncm5U) are required for wobble uridine-containing tRNAs to function efficiently in protein synthesis. Elongator is essential for mammalian development and defects in Elongator are associated with Familial Dysautonomia, a neurodevelopmental disease. The Elp1 component of yeast Elongator is phosphorylated by the casein kinase I orthologue Hrr25 and we have recently shown that Elongator-dependent U34 modification requires this phosphorylation. We are currently interested in understanding in molecular terms how Elp1 phosphorylation promotes Elongator function, and in particular whether Elp1 phosphorylation represents a mechanism that functions to regulate protein synthesis through modulating the functionality of U34-containing tRNAs. Elp1 contains a tRNA binding domain adjacent to the phosphorylated region and we would also like to understand whether there is a functional relationship between Elp1 phosphorylation and tRNA binding. Recent work in Archaea demonstrated that the archaeal orthologue of Elp3 is responsible for U34 modification. Since Archaea lack orthologues of the other five Elongator subunits that are essential for U34 modification in Eukaryotes, we are interested in understanding why U34 modification in higher organisms requires such complexity.
